Paroxysmal Nocturnal Hemoglobinuria (PNH) DONE BY : Basma Al Hag Ahmad Saja Abu Eida Sojood Abu Eita

Sings & symptoms Hemolysis Hypoxia . Jaundice . Splenomegaly . Weakness . Shortness of breath . Looking pale . Bone marrow failure . Cytopenias heavy renal tubular iron loading due to the continuous filtration of hemoglobin .

For urine : Increase urobilinogen . Hemoglobinuria . Black urine in color at morning ??. Hemosiderinuria . Albuminuria .

For Bone Marrow : May be normocellular to hypercellular with erythroid hyperplasia. * 50% of the nucleated cells may be normoblasts. May be hypocellular in concomitant BM failure. * Number of megakaryocytes may be decreased.

2-Confirmatory test : Sucrose Lysis Test Red cells absorb complement components from serum at low ionic concentrations . An iso-osmotic solution of sucrose (92.4g/l) is required . In PNH, lysis usually varies from 10% - 80% . Less specific for PNH; detects haemolysis associated with other blood-cell disorders . False negative in patients who have recently received a transfusion .

Paroxysmal - means "sudden and irregular“ , Nocturnal - means "at night“ and Hemoglobinuria - means "hemoglobin in urine . So, "paroxysmal nocturnal hemoglobinuria" means sudden, irregular episodes of passing dark colored urine, especially at night or in the early morning. The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to make hemolysis. However, this supposition was later disproved. Hemolysis has been shown to occur throughout the day and is not actually paroxysmal Hypoventilation Rise co2 In 1937, Thomas Ham reported that PNH erythrocytes were hemolyzed when incubated with normal, acidified serum.7 This seminal discovery resulted in the first diagnostic test for PNH, the acidified serum (Ham) test. The cell lysis following acidified serum appeared to be complement dependent because heat inactivation abrogated the reaction; however, it was not until 1954, with the discovery of the alternative pathway of complement activation, that complement was formally proven to cause the hemolysis of PNH red cells. In the 1980s, it was discovered that PNH cells display a global deficiency in a group of proteins affixed to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. Two of the missing GPI anchored proteins (CD55 and CD59) regulate complement. A few years later, a genetic mutation (phosphatidylinositol glycan class A [PIGA]) responsible for the GPI anchor protein deficiency was discovered,8⇓⇓-11 and most recently, a humanized monoclonal antibody that inhibits terminal complement activation has been shown to ameliorate hemolysis and thrombosis and improve quality of life in PNH patients.12

For Blood and CBC : Anemia and RBCs, may appear hypochromic and microcytic . ( due to iron def.) . WBCs and PLT may decrease . Occasional red cell fragments and anisopikilocytosis . ( thus mean RDW high ) . Nucleated red blood cells may be found . Reticulocytosis, is observed unless Bone Marrow Failure is severe . The leukopenia and thrombocytopenia is a consequence of Bone Marrow rather than complement-mediated destruction . DAT is negative

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